Genética do prognatismo mandibular: avaliação de heredogramas, análise complexa de segregação e análise de ligação com loci candidatos em famílias brasileiras averiguadas a partir de probandos afetados

AUTOR(ES)
DATA DE PUBLICAÇÃO

2006

RESUMO

There is a familial tendency to mandibular prognathism. Various genetic models have been described. It is assumed to be a polygenic trait in the vast majority of cases, with a threshold for expression. The purpose of the current study was to examine specific genetic models of the familial transmission of MP in Brazilian families and to search for evidences of linkage of six different microsatellite markers (D1S234, D4S3038, D6S1689, D7S503, D10S1483 and D19S566) located close to candidate regions. Study sample comprised 2606 individuals distributed in 55 families. Complete family histories for each proband were ascertained and the affection status of relatives were confirmed by lateral cephalograms, photographs and dental models. All the pedigrees were draw using PELICAN. Analysis showed major prevalence of MP in females when probands were included. The majority of the pedigrees suggest autosomal dominant inheritance. Incomplete penetrance was demonstrated by the observation of the proportion of unaffected parents and siblings of probands. Heritability of MP was estimated in 31.6%. Complex segregation analysis was performed using POINTER. Parts of some pedigrees were excluded to create 1-founder pedigrees, so final N was 2050. Segregation analysis indicated that there is a major gene that influences the outcome of mandibular prognathism with clear signs of Mendelian inheritance and a multifactorial component. For parametric linkage analysis, DNA was extracted from blood samples of 42 affected subjects, in 10 out of the original 55 families, amplified and genotyped with the GENOTYPER software (Perkin Elmer). Parameters were fixed for a dominant pattern of inheritance, with incomplete penetrance (90%) and 1% major gene allele frequency. The power of these pedigrees was estimated using SIMLINK. Two point LOD scores were calculated under a set of different values for θ, using the program MLINK. The data from all the families indicates that there is no evidence for linkage of any of the six microsatellite markers to a MP locus at θ = zero. For all the markers an exclusion region was delimited either direction, except for D4S3038 in which linkage couldnt be concluded nor excluded. The final results suggest that there should be locus heterogeneity for MP.

ASSUNTO(S)

microssatélites famílias brasileiras genética microsatellites. segregação brazilian families mandíbula ortodontia genetica mandibular prognathism linkage segregation analysis biologia animal ligação prognatismo mandibular

ACESSO AO ARTIGO

Documentos Relacionados